Kuzhikandathil E V, Molloy G R
Department of Biology, University of Delaware, Newark 19716, USA.
Glia. 1995 Dec;15(4):471-9. doi: 10.1002/glia.440150410.
The creatine kinase isoenzymes play an important role in maintaining ATP levels in some cell types during times of high energy demand. We have previously shown in primary cell cultures from rat brain that glial cells express much higher levels of brain creatine kinase (CKB) mRNA than neurons. In a separate earlier study we observed that transcription of CKB mRNA in glial cells can be stimulated by a forskolin-mediated increase in cAMP via a pathway involving protein kinase A (PKA). In this report, we show that the level of CKB mRNA in human U87 glioblastoma cells can be increased by either prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), or cholera toxin (an activator of G alpha s proteins). The induction of CKB mRNA occurs rapidly (with maximal induction after 6 h), is at the level of transcription, and is mediated specifically through PKA. In addition, the results indicate that both PGE1 and PGE2 use the same or related signal transduction pathways to increase CKB transcription. These results suggest that in glial cells CKB mRNA can be regulated by extracellular signals acting through G-protein-coupled receptors. This study may contribute to an understanding of the mechanisms underlying the previously-reported, early postnatal increase in CKB enzyme activity in rat brain. The results are also discussed with regard to the potential involvement of the expression of prostaglandins and CKB during hypoxia and ischemia.
在能量需求较高时，肌酸激酶同工酶在某些细胞类型中维持ATP水平方面发挥着重要作用。我们之前在大鼠脑原代细胞培养中发现，胶质细胞表达的脑型肌酸激酶（CKB）mRNA水平远高于神经元。在另一项早期研究中，我们观察到，通过蛋白激酶A（PKA）途径，福司可林介导的cAMP增加可刺激胶质细胞中CKB mRNA的转录。在本报告中，我们表明，人U87胶质母细胞瘤细胞中CKB mRNA的水平可通过前列腺素E1（PGE1）、前列腺素E2（PGE2）或霍乱毒素（Gαs蛋白激活剂）升高。CKB mRNA的诱导迅速发生（6小时后诱导达到最大值），发生在转录水平，且由PKA特异性介导。此外，结果表明PGE1和PGE2使用相同或相关的信号转导途径来增加CKB转录。这些结果表明，在胶质细胞中，CKB mRNA可受通过G蛋白偶联受体起作用的细胞外信号调节。本研究可能有助于理解先前报道的大鼠脑出生后早期CKB酶活性增加的潜在机制。还讨论了前列腺素和CKB表达在缺氧和缺血过程中的潜在作用。
